TREML4 mRNA Expression and Polymorphisms in Blood Leukocytes are Associated with Atherosclerotic Lesion Extension in Coronary Artery Disease

Victor Hugo Rezende Duarte,Adriana Augusto Rezende,Vivian Nogueira Silbiger,Maria Sanali Moura De Oliveira Paiva,Marcos Felipe De Oliveira Galvão,Isabelle Cristina Clemente Dos Santos,André Ducati Luchessi,Mychelle Kytchia Rodrigues Nunes Duarte,Mario Hiroyuki Hirata,Juliana Marinho De Oliveira,Ananília Medeiros Gomes Da Silva,Jéssica Nayara Góes De Araújo,Carolinne Thaisa De Oliveira Fernan Miranda,Marina Sampaio Cruz,Jéssica Cavalcante Dos Santos,Ayda Maria Quirino Silva Dos Santos,Rosario Dominguez Crespo Hirata

doi:10.1038/s41598-019-43745-y

TREML4 mRNA Expression and Polymorphisms in Blood Leukocytes are Associated with Atherosclerotic Lesion Extension in Coronary Artery Disease

Victor Hugo Rezende Duarte, Adriana Augusto Rezende + Show 15 more

Open Access

https://doi.org/10.1038/s41598-019-43745-y

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Abstract

Members of the triggering receptor expressed on myeloid cells (TREM) family are associated with atherosclerosis risk and progression. TREML4 is upregulated in the early phase of acute coronary syndrome. We investigated the relationship between the mRNA expression of 13 genes in blood leukocytes, TREML4 polymorphisms, and coronary artery lesion extension (Friesinger index) in patients with coronary artery disease (CAD) (n = 137). TREML4 rs2803495 (A > G) and rs2803496 (T > C) variants and leukocyte mRNA expression were analysed by qRT-PCR. TREML4 expression was higher in patients with major coronary artery lesions than in subjects without or with low and intermediate lesions (p < 0.05). However, TREML4 polymorphisms were not associated with coronary lesion extent. Presence of the rs2803495 G allele was not associated with increased TREML4 mRNA expression. Patients carrying the rs2803496 C allele (TC/CC genotypes) were more likely to express TREML4 mRNA than non-C allele carriers (allele C: OR 7.3, and 95% CI 1.9–27.5, p = 0.03). In conclusion, increased TREML4 mRNA expression in blood leukocytes is influenced by gene polymorphisms and is associated with more severe coronary artery lesions, suggesting its potential as a biomarker of the extent of coronary lesions in patients with CAD.

Highlights

Cardiovascular disease (CVD) remains among the leading causes of mortality and morbidity in developed and developing countries[1]
In a microarray-based study, we observed that the mRNA expression of 13 genes (ALOX15, AREG, BCL2A1, BCL2L1, CA1, COX7B, ECHDC3, IL18R1, IRS2, KCNE1, MMP9, MYL4, and TREML4) in blood leukocytes was increased within 2 h after the initial episode of acute coronary syndrome (ACS)
This study highlighted the association between TREML4 mRNA expression and polymorphisms as a potential biomarker for coronary lesion extent

Summary

Introduction

Cardiovascular disease (CVD) remains among the leading causes of mortality and morbidity in developed and developing countries[1]. In a microarray-based study, we observed that the mRNA expression of 13 genes (ALOX15, AREG, BCL2A1, BCL2L1, CA1, COX7B, ECHDC3, IL18R1, IRS2, KCNE1, MMP9, MYL4, and TREML4) in blood leukocytes was increased within 2 h after the initial episode of acute coronary syndrome (ACS). These genes were suggested as potential expression biomarkers for very early stages of ACS8. This study aimed to evaluate mRNA expression of the above 13 genes in peripheral blood leukocytes of patients with suspected CAD undergoing coronary angiography and to assess the association between TREML4 mRNA expression and polymorphisms as a potential biomarker for investigating the extent of coronary lesions

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